1. Field of the Invention
The present invention relates to a high-sensitivity nuclear magnetic resonance (NMR) spectrometer and also to a method of setting up the spectrometer.
2. Description of Related Art
A nuclear magnetic resonance (NMR) spectrometer is an analytical instrument for detecting signals of atomic nuclei having spin magnetic moments by applying a static magnetic field to these atomic nuclei to induce a Larmor precession in the spin magnetic moments and irradiating the atomic nuclei with RF waves having the same frequency as the Larmor precession so as to produce a resonance.
FIG. 1 is a schematic block diagram of an NMR spectrometer. This instrument includes an RF oscillator 1 producing RF waves which are controlled in phase and pulse width by a phase controller 2 and an amplitude controller 3. The resulting waves are sent as RF pulses to a power amplifier 4.
The RF pulses are amplified by the power amplifier 4 to a power level necessary to excite an NMR signal and then fed to an NMR probe 6 via a duplexer 5. The pulses are then directed at a sample under investigation from a transmit/receive coil (not shown) placed within the NMR probe 6.
After the RF pulse irradiation, a feeble NMR signal emanating from the sample is detected by the transmit/receive coil and sent to a preamplifier 7 via the duplexer 5. Then, the signal is amplified to a signal strength sufficient to be handled by a receiver 8.
The receiver 8 converts the frequency of the RF NMR signal amplified by the preamplifier 7 into an audio frequency that can be converted into digital form. At the same time, the amplitude is controlled. The NMR signal that has been converted into an audio frequency by the receiver 8 is converted into digital form by an analog-to-digital data converter (ADC) 9 and sent to a control computer 10.
The control computer 10 controls both phase controller 2 and amplitude controller 3. The computer also Fourier-transforms the NMR signal accepted in the time domain, phase-corrects the Fourier-transformed NMR signal, and then displays the corrected signal as an NMR spectrum.
An NMR spectrometer accurately detects local magnetic fields produced in nuclei under investigation using a detection coil. The obtained data about the magnetic fields include data about the external magnetic field and information about hyperfine magnetic fields produced from atoms existing in the surroundings. The hyperfine magnetic fields depend on the positions of atoms coordinated in the surroundings and on how the nuclei under investigation are coupled to surrounding atoms. Atomic-level chemical identification of samples and structural analysis of polymers (typified by proteins) are enabled by precisely analyzing the obtained magnetic field data.
In order to extract information about the hyperfine magnetic fields from the magnetic field data, it is important to achieve high-resolution spectra. For this purpose, it is important to achieve high homogeneity of the external magnetic field in the sample space. If the external magnetic field is made inhomogeneous for some reason or other, error occurs in extracting information about the hyperfine magnetic fields from the magnetic field data. One factor giving rise to inhomogeneous magnetic fields is the magnetization of instrument members close to the sample space. Especially, regarding a detection coil for detecting local magnetic fields, a disturbed magnetic field will be produced in the sample space by the coil unless its magnetization is null.
Usually, an NMR spectrometer characterized by high resolution is equipped with a shim coil set for correcting magnetic field distortions in the sample space. Realistically, however, the correction is restricted to low order spherical harmonic component of the magnetic field. Therefore, it is difficult to correct an inhomogeneous magnetic field due to the magnetization of the detection coil having a complex shape. Consequently, with respect to a detection coil having a complex shape and located close to the sample space, it is required that the magnetization of the material of the coil be reduced down to complete zero such that no magnetic field distortion is exerted into the sample space.
On the other hand, in order to enhance the accuracy of chemical identification and crystallographic structure determination, the sensitivity at which signals arising from nuclei under investigation are detected is important as well as resolution, needless to say. For example, if there exist many kinds of nuclei to be investigated having different hyperfine magnetic fields such as polymers, the correct molecular structure would not be derived unless all kinds of nuclei in small relative abundances can be detected.
Electromagnetic radiations detected by NMR spectroscopy lie in the RF range. The electromagnetic energy emitted by a single atom and detected by NMR is much weaker than energies of X-rays and light utilized by other techniques employing electromagnetic radiations. Contrivances (such as cross polarization) have been made to enhance weak signals. At the same time, methods of detecting weak signals at high sensitivity have been heretofore developed vigorously.
The method of detecting electromagnetic waves emanating from nuclei under investigation based on the Faraday's law of electromagnetic induction is a classical and well-known method. In a method using a detection coil based on the Faraday's law of electromagnetic induction, Johnson noises are prevalent among various types of noises according to the fluctuation-dissipation theorem. It is known that the noise level is in proportion to the square root of the temperature of the coil and to the square root of the electric resistance of the coil. Therefore, as mentioned, for example, in “High Temperature Superconducting Radio Frequency Coils for NMR Spectroscopy and Magnetic Resonance Imaging”, Steven M. Anlage, “Microwave Superconductivity”, ed. by H. Weinstock and M. Nisenoff, (Kluwer, Amsterdam, 2001), pp. 337-352, selecting the coil material from a superconducting material having an electrical resistance capable of being reduced down to substantially zero under cryogenic conditions is currently considered as one of the best methods among methods using detection coils based on the Faraday's law of electromagnetic inductance in enhancing the sensitivity at which NMR signals emanating from nuclei under investigation are detected.
In “Design, construction, and validation of a 1-mm triple-resonance high-temperature-superconducting probe for NMR”, William W. Brey et al., Journal of Magnetic Resonance 179 (2006) 290-293″, there is a mention of a detection coil which is made of a superconducting material and is promising as a signal detector having high sensitivity characteristics. The configuration and operation described in this document are described below. First, the whole configuration of the apparatus is shown in FIG. 2A. FIG. 2B is a cross section of a central portion of the apparatus.
A superconducting magnet system 21 applies a static magnetic field to a sample. The magnet system 21 is centrally provided with a bore extending vertically through the system along its axis. A cryogenic NMR probe 22 is mounted in this bore and has a sample loading portion around which a static magnetic field shimming system 23 (also referred to as the shim coil set) is disposed coaxially with the NMR probe 22. The shimming system 23 can produce magnetic fields having desired strength distributions in the X, Y, and Z directions in order to correct magnetic field distortions of the static magnetic field in the X, Y, and Z directions, the static magnetic field being applied to the sample. The NMR probe 22 is cooled by a coolant supplied from a probe cooling system 24.
FIG. 2B is a cross section of the cryogenic NMR probe 22, taken along a plane perpendicular to the axis of the static magnetic field H0. The probe 22 has a vacuum insulated pipe 33 in which a sample 32 is loaded. A coil element pair 31-1 for detection of 1H nucleus, a coil element pair 31-2 for detection of 2H nucleus (lock nucleus), a coil element pair 31-3 for detection of 13C nucleus, and a coil element pair 31-4 for detection of 15N nucleus are arranged in this order from the inside around the sample 32. Each detection coil is made of high temperature superconducting coil. Using high temperature superconducting materials, the coils have been fabricated on a flat substrate made of a ceramic of high thermal conductivity (such as sapphire or aluminum nitride). A pair of such coils constitutes a Helmholtz pair, placed on opposite sides of a sample. Each substrate is mounted to a base 30, which is cooled by the probe cooling system 24, and is held at a low temperature.
The cryogenic NMR probe 22 is characterized in that the detection coil is cooled cryogenically by the cooling capability of the probe cooling system 24 while controlling the sample 32 at a desired temperature by supplying a gas for adjustment of the temperature of the sample through the vacuum insulated pipe 33. This cooling lowers the electrical resistance of the detection coil and raises the Q value of the coil. Concomitantly, the electrical thermal noise drops. Because of their combined effects, it can be expected that the sensitivity at which NMR signals are detected will be enhanced.
Fabricating detection coils from a superconducting material as mentioned in the Anlage article cited herein, is intended to reduce the electrical resistance of the detection coils further and to improve the sensitivity further compared with the case where normal metal materials are used.
In discussing NMR utilization, it is expected that reduced RF surface resistances of superconductors will have the effect of suppressing thermal noise introduced to detection signals. However, a superconductor also has strong magnetic shielding effect concomitant with superconductivity. The superconductor exhibits diamagnetic character to magnetic flux expulsion, so-called the Meissner effect. Consequently, a strong magnetization is produced, disturbing the magnetic field homogeneity across the sample space. As a result, the magnetic field distortion near the detection coil reduces the detection coil filling factor which defines the fraction of the coil volume occupied by the sample. This leads to a deterioration in the signal/noice (S/N) ratio.
Anlage reported the characteristics of an NMR detection coil using a high-temperature superconductor. According to Table 1 of the Anlage article cited herein, a detection coil using a high-temperature superconductor at low temperatures shows Q values that are about 40 times as high as the Q values of detection coils made of normal metals such as copper at room temperature. Generally, the sensitivity at which an NMR signal is detected is in proportion to the square root of the Q value of a detection coil. Therefore, a calculation shows that the latter case provides a factor of about 6.3 improvement in sensitivity.
Table 1 of the Anlage article cited herein shows the filling factor normalized to that of the coil made of a normal metal in a room temperature environment. A coil made of a high-temperature superconductor in a low temperature environment has a filling factor of about 0.2. Generally, the sensitivity is in proportion to the square root of the filling factor. Therefore, in the latter case, the relative sensitivity coefficient is roughly halved to about 0.45.
One mentioned reason why the filling factor is so low is that a coil design using a flat substrate is urged. Another reason mentioned is that the detection coil is urged to be widely spaced from the sample 32 to avoid adverse effects of the magnetic field inhomogeneity because of strong magnetic shielding effect of a superconducting material.
U.S. Pat. Nos. 5,565,778 and 5,986,453 propose designs for achieving high Q-factor by employing a minimum of RF electric field over the sample volume. In these designs, the symmetry around the axis of the sample is enhanced, and slits are appropriately arranged to suppress shield currents becoming a magnetic shielding source due to the Meissner effect. However, it is difficult to take an appropriate countermeasure using slits around the axis of the external magnetic field. Furthermore, a decrease in the magnetic field homogeneity along the axis of the external magnetic field is inevitable.